The structure α-lipoic acid, with disulfide ring attached by a four-carbon chain to a carboxylic acid group, provides the molecule with unique biological activity. The amphiphilicity of the molecule allows it to penetrate lipid bilayers, including the blood-brain barrier while remaining limitedly soluble in aqueous environments. α-LA is one of the most powerful biological antioxidants and readily reduces reactive oxidant species in biological systems. Additionally, it plays a vital role in the enzymatic redox systems. The disulfide group readily complexes with metals and is a demonstrated chelating agent. Taking advantage of both the antioxidant and chelating properties, α-LA-palladium complexes are being used to protect against radiation poisoning. Additionally, α-LA supplementation has is commonly given to patients with Alzheimer's disease and diabetic neuropathy.

α-LA also shows anti-thrombotic properties. One example of exposed α-LA thiolane rings comes from Song and coworkers. Using carbodiimide-activated amidation, α-LA was attached to exposed amine groups on surface of a crosslinked 1,2-diaminocyclohexane coated stent. Platelet adhesion tests using AFM showed that very few platelets adhered to the α-LA-functionalized surfaces compared to the bare metal surface. The authors also discuss that the platelets on the α-LA-functionalized surface are not aggregated and therefore would be less prone to clotting in vivo. These results are supported by a previous study that indicates α-LA inhibits the expression of adhesive molecules in some cells. Platelet adhesion to the crosslinked polymer before α-LA functionalization was not shown.
Redox-sensitive disulfide bonds are an invaluable tool in the design of drug delivery vesicles. The disulfide bond may formed or maintained under mildly oxidizing conditions, such as that found in the slightly basic bloodstream. In reducing environments, such as those found in the cell cytosol and lysosome compartments, disulfide bonds are cleaved to form thiol groups. Disulfide cleavage is accelerated in these environments by enzymes specific to disulfide cleavage. In drug delivery, this means that therapeutic agents maybe trapped in vesicles under mild conditions, continue to be protected while circulating in the body and then be released upon endocytosis. Additionally, crosslinking of self-assembled vesicles, like micelles and liposomes, reduces susceptibility to shear-induced disassembly. The importance of reduction-sensitive vesicles is demonstrated by several review papers.
The resulting reactive thiolate anions formed upon reduction may, however be harmful to the cell. A-LA presents a unique solution to the problem; upon reduction of α-LA crosslinks the resulting dithiolate compound readily reforms the disulfide ring while at the same time reducing a neighboring oxidized species. Separated by four methylene groups from the thiolane ring, the sterically unhindered carboxylic acid group facilitates conjugation to a wide variety of molecules, including peptides, carbohydrate polymers and phospholipids.
Biochemists L. J. Reed and C.-I. Niu first reported the presence of poly(DL-α-LA) in 1955 where it was a byproduct in their synthesis of DL-α-lipoic acid. The following year, Thomas and Reed published an account of the purposeful, thermally-induced polymerization of the disulfide, however the focus of the paper was on the subsequent depolymerization of the polymer to desired DL-α-LA rather than the characterization of the polymer. DL-α-lipoic acid was heated to at 65° C. for fifteen minutes to produce a colorless polymer. The reaction reached monomer conversion of 52%. The next report of α-LA polymerization is from 1980 and used tributylphosphine (TBP) with α-LA in an acetonitrile solution. Rather than polymerize through the disulfide bonds as shown below, this reaction forms poly(thio-1-oxo-6-mercaptooctamethylene) in which the α-LA units are connected via a thioester bond (see below). The pendant thiol group was acetylated to prevent crosslinking through oxidation. Based on polystyrene standards, the number average molecular weight (Mn) of the acetylated polymer was 8,400 g/mol.

The group of Kiyoshi Endo has been investigating the ring-opening polymerization of cyclic disulfides, including α-LA, for the last decade. Copolymers of α-LA and 1,2-dithiane (DT) of varying molar ratios were thermally polymerized in bulk conditions under high vacuum. Monomer conversion, molecular weights and polydispersity index all increased with increasing α-LA monomer content. An exception to the trend was a slight decrease in Mn for the 100% α-LA homopolymer which reached 416,000 g/mol. The highest molecular weight was found for the 70% α-LA copolymer which had an Mn of 550,000 g/mol (based on polystyrene standards). The authors propose a catenane structure for the copolymers with the interlocking cyclic structures averaging about 5,000 g/mol. These copolymers were later dissolved in pyridine and crosslinked with zinc (II) acetate at room temperature.
Endo and coworkers also investigated the homopolymerization of α-LA on its own. The thermal polymerization was again carried out under high vacuum in bulk conditions. Polymers were not obtained below the melting temperature of the crystalline monomer, but readily polymerized at elevated temperatures with conversion and molecular weight increasing with increasing temperature. Polymers from the reaction carried out at 90° C. reached Mn of 1,370,000 g/mol with a PDI of 1.5 and 66.8% conversion. The catenane structure proposed for the polymer consists of interlocking cyclic polymers of Mn=12,000 g/mol. Their assessment of the cyclic ring stems from the GPC analysis of the UV degradation products of higher molecular weight polymers and from polymerizing α-LA in the presence of cyclic poly(ethylene glycol) derivatives.